ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/056/SRR30920156/SRR30920156_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/055/SRR30920155/SRR30920155_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/057/SRR30920157/SRR30920157_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/055/SRR30920155/SRR30920155_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/057/SRR30920157/SRR30920157_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR309/056/SRR30920156/SRR30920156_1.fastq.gzprimaryOK200GenomicsBiological Sciences, IISER Mohalihttps://www.ebi.ac.uk/ena/browser/view/PRJNA1169897Mus musculusxref:PubMed:39604443Here, we demonstrate that Rab8a, a small GTPase, plays critical role in the functioning of dendritic cells (DCs) of aging host. Compared with the cells of young mice, CD11c+CD11b+ bone marrow derived dendritic cells (BMDCs) of aged mice generated a diminished type I IFN response when stimulated with Influenza A virus (IAV) and murine herpesvirus 68 (MHV68). In comparison to those of young mice, BMDCs of aged mice inefficiently presented exogenous antigens to CD8+ T cells in vitro and in vivo. While the Rab8a overexpressing BMDCs of aged animals regained functionality and generated a potent anti-viral IFN response, the Rab8a depleted cells of young animals were severely compromised in producing IFNs. BMDCs of young and aged animals were transcriptionally distinct but the Rab8a overexpressing cells of aged animals widely shared transcriptome with those of young animals. Ovalbumin fed Rab8a reconstituted BMDCs of aged animals upregulated Rab11 than did the control cells. Both Rab8a and Rab11 preferentially co-localised with the generated SIINFEKL peptide-H-2Kb complexes in the endosomal recycling compartment (ERC) to efficiently induce the surface display of such complexes. Compared with the control cells, the Ova fed Rab8a reconstituted BMDCs of aged animals expanded more of the TCR tg OT1 cells to better control IAV (WSN-SIINFEKL) infection. Therefore, targeting Rab8a might serve as a strategy to promote the functioning of DCs in the aging host to achieve favourable outcome of viral infection. Overall design: Aged Bone marrow cells transduced with lentiviruses for Rab8a overexpression and untransduced Young and Aged Bone marrow cells were cultured in the presence of IL4 and GMCSF for 5 days. The CD11b+CD11c+ cells were then sorted for RNA isolation and sequencing.ENACR3A, 3.4.22.-, Dendritic Cells, Laboratory, Interdigitating, ATRABE1C, Mus domesticus, cell surface glycoprotein MAC-1 subunit alpha, mini-ICE, CASP-14, RAB GTPase homolog 8A, 95, House Mouse, ARA3, Leukocyte adhesion receptor MO1, House, Mus musculus domesticus, Interdigitating Dendritic Cell, Dendritic Cell, Interstitial Dendritic Cell, Mice, 95 alpha chain, Mac-1a, MAC-1, Plasmacytoid Dendritic, Swiss, Interdigitating Dendritic, Dendritic, neutrophil adherence receptor, Plasmacytoid, Leukocyte adhesion glycoprotein p150, Swiss Mice, Leu M5, leukocyte adhesion glycoprotein p150, Interstitial Dendritic, CD11 antigen-like family member B, N418, CD11 antigen-like family member C, ARA-3, MO1A, Mac-1, CR-3 alpha chain, Interstitial Dendritic Cells, RAB8, ITGAM, Cr4, Veiled Cells, AA409338, ATRAB8A, CD11c, CD11b, AI449405, Neutrophil adherence receptor, mouse, ITGAX, Interstitial, Cell, Plasmacytoid Dendritic Cells, CR3, Mus, Mini-ICE, Mel, MEL, Mus musculus., MAC1, Mus musculus, MAC1A, Plasmacytoid Dendritic Cell, SMALL GTP-BINDING PROTEIN, Caspase-14 subunit p10, Veiled Cell, mice, Veiled, Interdigitating Cells, Swiss Mouse, House Mice, Caspase-14 subunit p19, CD11b/CD18, MICE, Laboratory Mice, domesticus, F730045J24Rik, leukocyte adhesion receptor p150, Cell surface glycoprotein MAC-1 subunit alpha, CD11C, CD11B, Cells, leukocyte adhesion receptor MO1, Interdigitating Dendritic Cells, Leukocyte adhesion receptor p150, Interdigitating Cell, Mouse, SLEB6, Ly-40, Laboratory Mouse, Cd11c, Elderly, Cd11bCR3A, 3.4.22.-, Dendritic Cells, Laboratory, Interdigitating, ATRABE1C, Mus domesticus, cell surface glycoprotein MAC-1 subunit alpha, mini-ICE, CASP-14, RAB GTPase homolog 8A, 95, House Mouse, ARA3, Leukocyte adhesion receptor MO1, House, Mus musculus domesticus, Interdigitating Dendritic Cell, Dendritic Cell, Interstitial Dendritic Cell, Mice, 95 alpha chain, Mac-1a, MAC-1, Plasmacytoid Dendritic, Swiss, Interdigitating Dendritic, Dendritic, neutrophil adherence receptor, Plasmacytoid, Leukocyte adhesion glycoprotein p150, Swiss Mice, Leu M5, leukocyte adhesion glycoprotein p150, Interstitial Dendritic, CD11 antigen-like family member B, N418, CD11 antigen-like family member C, ARA-3, MO1A, Mac-1, CR-3 alpha chain, Interstitial Dendritic Cells, RAB8, ITGAM, Cr4, Veiled Cells, AA409338, ATRAB8A, CD11c, CD11b, AI449405, Neutrophil adherence receptor, mouse, ITGAX, Interstitial, Cell, Plasmacytoid Dendritic Cells, CR3, Mus, Mini-ICE, Mel, MEL, Mus musculus., MAC1, Mus musculus, MAC1A, Plasmacytoid Dendritic Cell, SMALL GTP-BINDING PROTEIN, Caspase-14 subunit p10, Veiled Cell, mice, Veiled, Interdigitating Cells, Swiss Mouse, House Mice, Caspase-14 subunit p19, CD11b/CD18, MICE, Laboratory Mice, domesticus, F730045J24Rik, leukocyte adhesion receptor p150, Cell surface glycoprotein MAC-1 subunit alpha, CD11C, CD11B, Cells, leukocyte adhesion receptor MO1, Interdigitating Dendritic Cells, Leukocyte adhesion receptor p150, Interdigitating Cell, Mouse, SLEB6, Ly-40, Laboratory Mouse, Cd11c, Elderly, Cd11bfalseRab8a restores diverse innate functions of CD11b+CD11c+ dendritic cells from aged miceRab8a restores diverse innate functions of CD11b+CD11c+ dendritic cells from aged mice2025-09-242024-10-18PRJNA1169897GSE2790031009039604443